Effect of Non-electrolytes on the Cloud Point and Dye Solubilization of Antidepressant Drug, Clomipramine Hydrochloride

Clomipramine hydrochloride (CLP, an amphiphilic drug) solutions, prepared in sodium phosphate buffer, show temperature dependent phase separation (commonly known as Cloud Point, CP). CP can be varied with the help of additives. Hence, in this paper we are reporting the effect of various additives on the CP of CLP. Alcohols affect in two ways: CP either remains constant (or increases slightly) or decreases. Short chain alcohols remain soluble in aqueous phase and CP remains nearly constant in their presence as alcohol-water mixed system proves better solvent for the drug. Long chain alcohols, due to their hydrophobic nature, partition into the drug micelles and cause micellar growth which, in turn, decreases the CP. Sugars enhance the hydrophobic forces and decrease the CP. CP with amino acids is found to be nature dependent: acidic amino acids and hydrochloride salts of basic amino acids increase the CP (due to the interaction of their negatively charged side chains with the drug molecules). Basic amino acids decrease the CP. With polar and uncharged polar amino acids, CP remains constant. This last class of amino acids either remains in the bulk phase or solubilizes inside the micelle, and in either case, the hydration of micelles, and the CP, remain unaffected.